Natural history of precancerous and early cancerous lesions of the uterine cervix

A prospective study of cervical dysplasia cases and control cases matched for age and parity was undertaken in search of factors related to cervical carcinogenesis. Cytologic examination of 66,736 women revealed negative findings in 28.5%, inflammation in 70.3%, dysplasia in 1.4% and carcinoma in 0.1% of the cases. Data on epidemiologic features, cytomorphologic characteristics and serologic findings of antibodies to herpes simplex virus (HSV) were collected for proven cancer patients, dysplasia cases and control subjects. Cancer patients revealed significantly elevated antibodies to HSV as compared to the controls. The analysis revealed a higher proportion of dysplasia cases with an age at consummation of marriage of less than or equal to 15 years as compared to controls, with a relative risk of 1.5 (P less than .05). Similarly, a higher proportion of women with dysplasia had HSV-II-specific antibodies as compared to control women. The relative risk was found to be 1.3, which was not statistically significant (P greater than .05). The Mantel-Haenszel summary relative risk between antibodies to HSV and the two groups (dysplasia cases and controls), adjusted for the age at consummation of marriage, worked out to be 1.38, which was also statistically not significant (P greater than .05). The overall progression rate of dysplasia to malignancy was found to be 11.7% at the end of 54 months (during a total follow-up period of 84 months). Progression to cancer was highest in severe dysplasia cases and less in mild dysplasia cases. The progression rates were also significantly higher in the group of women who revealed antibodies to HSV II. Similar differences in the progression rates were observed with regard to the age at consummation of marriage.     

Human complementary component C′3

Summary Results obtained so far on the C3 polymorphism suggest that the system should be a valuable marker in population studies. The instability of the complement component C3 may, however, cause some practical problems in population genetic fieldwork, since a certain fraction of serum samples may be difficult to type with certainty due to storage alterations. Studies of the conversion rate and the concentration of C3 have shown that there is no significant difference between the phenotypes. And furthermore, the fact that there is good agreement with the Hardy-Weinberg distribution indicates that the conversion has had no appreciable selective effect on the phenotype distribution (Brönnestam et al., 1971).     

Relative Importance of H2 and H2S as Energy Sources for Primary Production in Geothermal Springs

Geothermal waters contain numerous potential electron donors capable of supporting chemolithotrophy-based primary production. Thermodynamic predictions of energy yields for specific electron donor and acceptor pairs in such systems are available, although direct assessments of these predictions are rare. This study assessed the relative importance of dissolved H₂ and H₂S as energy sources for the support of chemolithotrophic metabolism in an acidic geothermal spring in Yellowstone National Park. H₂S and H₂ concentration gradients were observed in the outflow channel, and vertical H₂S and O₂ gradients were evident within the microbial mat. H₂S levels and microbial consumption rates were approximately three orders of magnitude greater than those of H₂. Hydrogenobaculum-like organisms dominated the bacterial component of the microbial community, and isolates representing three distinct 16S rRNA gene phylotypes (phylotype = 100% identity) were isolated and characterized. Within a phylotype, O₂ requirements varied, as did energy source utilization: some isolates could grow only with H₂S, some only with H₂, while others could utilize either as an energy source. These metabolic phenotypes were consistent with in situ geochemical conditions measured using aqueous chemical analysis and in-field measurements made by using gas chromatography and microelectrodes. Pure-culture experiments with an isolate that could utilize H₂S and H₂ and that represented the dominant phylotype (70% of the PCR clones) showed that H₂S and H₂ were used simultaneously, without evidence of induction or catabolite repression, and at relative rate differences comparable to those measured in ex situ field assays. Under in situ-relevant concentrations, growth of this isolate with H₂S was better than that with H₂. The major conclusions drawn from this study are that phylogeny may not necessarily be reliable for predicting physiology and that H₂S can dominate over H₂ as an energy source in terms of availability, apparent in situ consumption rates, and growth-supporting energy.     

Three-dimensional structure of a putative non-cellulosomal cohesin module from a Clostridium perfringens family 84 glycoside hydrolase

The genomes of myonecrotic strains of Clostridium perfringens encode a large number of secreted glycoside hydrolases. The activities of these enzymes are consistent with degradation of the mucosal layer of the human gastrointestinal tract, glycosaminoglycans and other cellular glycans found throughout the body. In many cases this is thought to aid in the propagation of the major toxins produced by C. perfringens. One such example is the family 84 glycoside hydrolases, which contains five C. perfringens members (CpGH84A-E), each displaying a unique modular architecture. The smallest and most extensively studied member, CpGH84C, comprises an N-terminal catalytic domain with β-N-acetylglucosaminidase activity, a family 32 carbohydrate-binding module, a family 82 X-module (X82) of unknown function, and a fibronectin type-III-like module. Here we present the structure of the X82 module from CpGH84C, determined by both NMR spectroscopy and X-ray crystallography. CpGH84C X82 adopts a jell-roll fold comprising two β-sheets formed by nine β-strands. CpGH84C X82 displays distant amino acid sequence identity yet close structural similarity to the cohesin modules of cellulolytic anaerobic bacteria. Cohesin modules are responsible for the assembly of numerous hydrolytic enzymes in a cellulose-degrading multi-enzyme complex, termed the cellulosome, through a high-affinity interaction with the calcium-binding dockerin module. A planar surface is located on the face of the CpGH84 X82 structure that corresponds to the dockerin-binding region of cellulolytic cohesin modules and has the approximate dimensions to accommodate a dockerin module. The presence of cohesin-like X82 modules in glycoside hydrolases of C. perfringens is an indication that the formation of novel X82-dockerin mediated multi-enzyme complexes, with potential roles in pathogenesis, is possible.